Best Treatment for CLL

[Rrriver]

Is Zanubrutinib a better treatment than Acalabrutinib for CLL because it is the newest approved version for BTK drugs.

[Jm954 Administrator]

Yes, regarded as better as more tolerable, less side effects and that leads to better compliance.

Trial results were all in favour of Zanubrutinib for both relapsed CLL and first treatment (although it was against bendamustine). This is the results of the head to head study against Ibrutinib which was for relapsed but no reason to think it would perform worse for the treatment naive group.

ashpublications.org/blood/a...

Jackie

[Rrriver]

Thanks, I read that Z stays in your system for the entire time between doses while A dissipates after a few hours till the next dose , therefore Z is going after cancer cells continuously.

[flipperj]

I have taken both and I would say definitely not. Zanubrutinib being a little later to obtain a label for CLL doesn’t necessarily make it better than Acalabrutinib. There is no head to head data for the two that I’m aware of. Acalabrutinib has a cleaner profile with less off target inhibitions while Zanubrutinib has more effective blocking in tissues. For me, Zanubrutinib came with more side effects but it has been more effective than Acalabrutinib. Keep in mind drug elimination half life does not correlate to BTK blocking duration for covalent drugs.

[bennevisplace in reply to flipperj]

There can't be many CLL patients to have tried both Acalabrutinib and Zanubrutinib. Please tell us more.

[kitchengardener2]

I can't comment on Z but I have been taking Acalabrutinib since August 2021 with great success. Long may it last.

[Edalv]

I have not taken Acalabrutinib nor Zanubrutinib, but for all I have read I came to the simple conclusion that it probably depends on the patient and the characteristics of CLL on that particular patient. That’s why it should be consulted with a CLL specialist before embarking on a particular treatment. We are lucky in many ways to have all these choices available and others under active study as single agents or in combination. The other benefit of having multiple treatment options is that if one agent doesn’t work, another different one might. Stay strong, and peace to all… 🙏

[flipperj in reply to Edalv]

I think you are right. Side effect profiles are a little different for each drug. Some will have a better experience on Acalabrutinib and others with Zanubrutinib. These drugs were developed in parallel to compete with Ibrutinib. I think when a head to head study is done between A and Z, there will be a wholesale shift to Z due to increased effectiveness. This is just speculation on my part. I know advocates of BTKis like Furman have already done so based on their clinical experience.

[rvles]

What do you mean by "better"? More effective? Fewer side effects? Over what time frame, knowing that we don't have the long term (10 years and more) picture? For which type of CLL, mutated, unumated, 13Q, 17p,etc..? There are too many variables to be able to say that one drug is "better" than another. It's best to figure out your treatment objectives and constraints, learn about the different treatments, consult with you doctor and decide which one fits best with your individual situation.

[SeymourB]

Rrriver -

To my knowledge, acalabrutinib and zanubrutinib have not gone head to head in a trial. Doctors can try to compare individual trial results of a large number of patients. There have been many more acalabrutinib trials than zanubrutinib, and even comparing 2 acal trials with each other can lead to conflicting results due to the demographics of the patients. So a head to head is still the gold standard.

But ibrutinib and zanubrutinib have been compared - the ALPINE trial:

futuremedicine.com/doi/full...

ALPINE: zanubrutinib versus ibrutinib in relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma

Published Online:24 Mar 2020

More readable, perhaps:

onclive.com/view/final-resp...

First Response Analysis of ALPINE Trial Shows Superior ORR With Zanubrutinib Vs Ibrutinib in CLL

Apr 11, 2022

They were pretty close in some respects, but the relative difference in Afib and compliance (people staying on the drug despite adverse effects) was enough that the NCCN (National Comprehensive Cancer Network) in the U.S. removed Ibrutinib from preferred status. Acalabrutinib and zanubrutinib are now the preferred BTKi's. Venetoclax and Obinutuzumab are also still listed as preferred.

In various webinars that I've seen, doctors mention moving from ibrutinib or acalabrutinib to zanabrutinib only if experiencing adverse effects. That could be as little as "it tastes funny" or as serious as a hospitalization due to stroke, I think.

I haven't heard any public debate on moving from zanubrutinib to ibrutinib or acalabrutinib.

=seymour=

[flipperj]

For Acalabrutinib, the elimination half life for the parent drug is about an hour but the BTK blocking is maintained for well over 24 hrs. Acalabrutinib was dosed once daily in the initial clinical studies with success. Twice daily dosing is a small theoretical advantage but likely not clinically significant according to the investigators. Similar situation for Zanubrutinib. The elimination time for the drug does not necessarily correlate to the period of BTK effect.

I think the primary advantage to Zanubrutinib is the superior BTK occupancy in the lymph nodes. I noticed a difference within days. The side effect profiles are really a toss up according to my doctor and this has been my experience. One is not necessarily better than the other, they are just a bit different.

[flipperj]

Yes, due to the covalent nature of the binding. BTK itself has a half life and regeneration cycle which tends to be more of a factor in setting a dosing schedule for the covalent drugs. It can actually be an advantage for a drug to be fast in and fast out so to speak to manage toxicity.